NPC Archive Item: Sedatives, hypnotics and antidepressants associated with an increased risk of falling in older people

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4 January 2010

A meta-analysis has found that, in people older than 60 years, benzodiazepines, other sedatives and hypnotics, and antidepressants are associated with an increased risk of falling of around 50-70% in relative terms. Antihypertensives and NSAIDs may also be associated with a smaller, but still significant increased risk of falling.

Level of evidence:
Level 2 (limited quality patient-oriented evidence) according to the SORT criteria

Action
Healthcare professionals should follow the NICE guideline on the assessment and prevention of falls in older people. NICE gives advice on case identification and multifactorial falls risk assessment and recommends that all older people with recurrent falls, or assessed as being at increased risk of falling, should be considered for an individualised multifactorial intervention, including strength and balance training, home hazard assessment and intervention, vision assessment and referral, and medication review with modification or withdrawal.

This study suggests that particular attention should be paid to reviewing the use of benzodiazepines, other sedatives and hypnotics, and antidepressants. Antihypertensives may also increase the risk of falling. In addition, there is some evidence from a subgroup analysis, which considered ‘good’ studies only, that antipsychotics and NSAIDs may also be associated with an increase in falls.

What is the background to this?
Falls are a major cause of disability and the leading cause of mortality resulting from injury in people aged above 75 years in the UK. It is estimated that one in three people aged 65 years and over experience a fall at least once a year, rising to one in two among those aged 80 years and over. Although most falls result in no serious injury, approximately 5% of older people living in the community who fall in a given year experience a fracture or require hospitalisation. Furthermore, up to 14,000 people die annually in the UK as a result of an osteoporotic hip fracture. Incidence rates for falls in nursing homes and hospitals are two to three times greater than in the community and complication rates are also considerably higher.

Many factors can impact on the risk of falls and fractures including physical activity level, muscle strength, maintenance of balance while upright, visual impairment and use of several commonly prescribed medications such as psychotropic drugs. This study aimed to update previous meta-analyses which looked at the association between medication use and falling.

What does this study claim?
In people aged 60 years and older, the use of benzodiazepines, other sedatives and hypnotics and antidepressants was associated with a significant increase in falls (see study details below).

So what?
The meta-analysis has limitations. Firstly, the results are based only on observational data which are subject to bias. In addition, as the authors point out, relatively few studies met the inclusion criteria of using falls as an outcome. However, although the number of new studies included was small for every drug class assessed besides diuretics, the total number of participants included was higher than in previous meta-analyses. A further limitation was the method of ascertaining falls and medication in many of the studies. Several types of analysis were carried out, for example, Bayesian pooled estimates (adjusted and unadjusted), random-effects pooled estimates and various subgroup analyses. However, not all analyses were carried out for all nine drug classes; therefore the data are difficult to interpret. Nevertheless, the meta-analysis provides reasonable evidence to demonstrate that benzodiazepines, other sedatives and hypnotics, and antidepressants are associated with an increased risk of falling and provides a useful reminder that medication review is an important part of risk assessment for falling.

The NICE clinical guideline on the assessment and prevention of falls in older people (>65 years) provides advice on case identification and multifactorial falls risk assessment. It recommends that older people should be asked routinely whether they have fallen in the past year and asked about the frequency, context and characteristics of the fall/s. In addition, older people reporting a fall or considered at risk of falling should be observed for balance and gait deficits and considered for their ability to benefit from interventions to improve strength and balance.

All older people with recurrent falls, or assessed as being at increased risk of falling, should be considered for an individualised multifactorial intervention, including strength and balance training, home hazard assessment and intervention, vision assessment and referral, and medication review with modification or withdrawal. In particular, older people on psychotropic medications should have their medication reviewed, with specialist input if appropriate, and discontinued if possible to reduce their risk of falling.  This meta-analysis supports this recommendation. Following treatment for an injurious fall, older people should be offered a multidisciplinary assessment to identify and address future risk, and individualised intervention aimed at promoting independence and improving physical and psychological function.

A suite of educational materials on osteoporosis, including a <60minute eLearning event, is now available on NPC. In addition a MeReC Bulletin, which describes the management of a postmenopausal woman with risk factors for osteoporosis in a case-study format, will be available at the end of January 2010. This illustrates use of the two NICE technology appraisals on drug treatments for primary and secondary prevention of osteoporotic fragility fractures in postmenopausal women and outlines some issues for healthcare professionals to consider.

Study details:
Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med 2009;169:1952–60

Design: Twenty-two studies were included. None were randomised controlled trials. Ten were cohort studies, 5 were case-control studies and 7 were cross-sectional studies. Meta-analyses, including 79,081 participants, were completed on 9 drug classes.

Patients: Aged 60 years and over.

Intervention and comparison: The meta-analysis assessed the association between medication use and falls

Outcomes and results: The results of a previous meta-analysis were combined with the new information obtained to estimate updated Bayesian odds ratios (ORs) and 95% credible intervals (CrI) (the Bayesian equivalent of 95% confidence intervals [95%CI]). A subset of studies provided adjusted ORs for the drug classes included in this meta-analysis. Pooled adjusted ORs were similar to the adjusted ORs suggesting that the role confounding by indication was low in the study. The unadjusted and adjusted OR estimates are shown in the table below.

Unadjusted Adjusted
Drug class OR 95%CI Significant OR 95%CI SIgnificant
Antihypertensives 1.24 1.01 to 1.50 Yes Not available
Diuretics 1.07 1.01 to 1.14 Yes 0.99 0.78 to 1.25 No
Beta-blockers 1.01 0.86 to 1.17 No Not available
Sedatives/hypnotics 1.47 1.35 to 1.62 Yes Not available
Neuroleptics/antipsychotics 1.59 1.37 to1.83 Yes 1.39 0.94 to 2.00 No
Antidepressants 1.68 1.47 to 1.91 Yes 1.36 1.13 to 1.76 Yes
Benzodiazepines 1.57 1.43 to 1.72 Yes 1.41 1.20 to 1.71 Yes
Narcotics 0.96 0.78 to 1.18 No Not available
NSAIDs 1.21 1.01 to 1.44 Yes Not available

After adjusting for confounders, an increased likelihood of falling was associated with use of benzodiazepines and antidepressants. The use of diuretics or neuroleptics/antipsychotics was associated with a statistically significant increased risk of falls in the unadjusted meta-analysis. However, after adjustment for other confounders they were not statistically significantly associated with falling. Adjusted figures were not available for antihypertensives, beta-blockers, sedatives/hypnotics, narcotics or NSAIDs.

Random effects meta-analysis also identified statistically significant increases in the risk of falls  with the use of antihypertensives, sedatives/hypnotics, neuroleptics/antipsychotics, antidepressants, and  benzodiazepines, but not beta-blockers, diuretics, narcotics or NSAIDs.

When a subgroup analysis was performed of studies that had ‘good’ medication and falls ascertainment, an increased likelihood of falling was estimated for the use of sedatives and hypnotics, neuroleptics and antipsychotics, antidepressants, benzodiazepines, and NSAIDs.

Sponsorship: The Canadian Institutes of Health Research, The Michael Smith Foundation for Health Services Research and the Government of Canada Research Chair in Pharmaceutical Outcomes.

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